Effect of Kinases in Extracellular Vesicles from HIV-1-Infected Cells on Bystander Cells

Cells, Journal Year: 2025, Volume and Issue: 14(2), P. 119 - 119

Published: Jan. 15, 2025

As of 2023, there were 39.9 million people living with Human Immunodeficiency Virus type 1 (HIV-1). Although great strides have been made in treatment options for HIV-1, and our understanding the HIV-1 life cycle has vastly improved since start this global health crisis, a functional cure remains elusive. One main barriers to is latency, which allows virus persist despite combined antiretroviral therapy (cART). Recently, we found that exosomes, are small, membrane-enclosed particles released by virtually all cell types known mediate intercellular communication, caused an increase RNA Polymerase II loading onto promoter. This resulted production both short- long-length viral transcripts infected cells under cART. current study examines effects exosome-associated kinases on bystander cells. The phospho-kinase profiling exosomes revealed differences kinase payload derived from uninfected HIV-1-infected cells, CDK10, GSK3β, MAPK8 having largest concentration differences. These shown be biologically active capable phosphorylating substrates, they modulated changes dynamics exposed Given relevance such immune response, results implicate as new possible key contributors pathogenesis affect findings may guide therapeutic avenues improve regimens.

Language: Английский

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Exosomal mir-126-3p derived from endothelial cells induces ion channel dysfunction by targeting RGS3 signaling in cardiomyocytes: a novel mechanism in Takotsubo cardiomyopathy

Stem Cell Research & Therapy, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 4, 2025

Abstract Background Takotsubo cardiomyopathy (TTC) is marked by an acute, transient, and reversible left ventricular systolic dysfunction triggered stress, with endothelial being one of its pathophysiological mechanisms. However, the precise molecular mechanism underlying interaction between cells cardiomyocytes during TTC remains unclear. This study reveals that exosomal miRNAs derived from exposed to catecholamine contribute ion channel in setting TTC. Methods Human-induced pluripotent stem cell-derived (hiPSC-CMs) were treated epinephrine (Epi) or exosomes (Exo) Epi-treated human cardiac microvascular (HCMECs) Exo HCMECs transfected miR-126-3p. The immunofluorescence staining, flow cytometry, qPCR, single-cell contraction, intracellular calcium transients, patch-clamp, dual luciferase reporter assay western blot performed for study. Results Modeling high doses treatment hiPSC-CMs shows suppression depolarization velocity (Vmax), prolongation action potential duration (APD), induction arrhythmic events. Epi (Epi-exo) mimicked enhanced effects Epi. exposure led elevated levels miR-126-3p both their exosomes. enriched demonstrated similar as Epi-exo, establishing crucial role Epi-exo. Dual coupled gene mutation techniques identified was found target regulator G-protein signaling 3 (RGS3) gene. Western qPCR analyses confirmed miR-126-3p-mimic reduced RGS3 expression hiPSC-CMs, indicating inhibits signaling. Additionally, significantly higher serum patients compared healthy controls who had recovered Conclusions Our first reveal miR-126-3p, originating cells, contributes regulating cardiomyocytes. These findings provide new perspectives on pathogenesis suggest therapeutic targets treatment. Graphical

Language: Английский

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Inflammation pathways as therapeutic targets in angiotensin II induced atrial fibrillation

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 16

Published: March 3, 2025

Atrial fibrillation (AF), a common cardiac arrhythmia, is associated with severe complications such as stroke and heart failure. Although the precise mechanisms underlying AF remain elusive, inflammation acknowledged pivotal factor in its progression. Angiotensin II (AngII) implicated promoting atrial remodeling inflammation. However, exact pathways through which AngII exacerbates are still not fully defined. This study explores key molecular involved, including dysregulation of calcium ions, altered connexin expression, activation signaling TGF-β, PI3K/AKT, MAPK, NF-κB/NLRP3, Rac1/JAK/STAT3. These instrumental contributing to fibrosis, electrical remodeling, increased susceptibility AF. Ang II-induced disrupts ion channel function, resulting structural atria significantly elevating risk Anti-inflammatory treatments RAAS inhibitors, colchicine, statins have demonstrated potential reducing incidence AF, although clinical outcomes inconsistent. manuscript underscores link between AngII-induced development proposing importance targeting management

Language: Английский

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Exosome-Based Therapy in Cardiovascular Diseases: A New Frontier in Cardiovascular Disease Treatment

Korean Circulation Journal, Journal Year: 2025, Volume and Issue: 55

Published: Jan. 1, 2025

Exosomes, small extracellular vesicles ranging from 30 to 150 nanometers in diameter, have emerged as pivotal mediators of intercellular communication. These vesicles, originally perceived cellular debris, are now recognized for their intricate roles transporting bioactive molecules, including proteins, lipids, and nucleic acids, between cells. Exosomes received considerable attention due diverse physiological pathological processes, especially relation cardiovascular diseases (CVDs). CVDs intricately linked, sharing common risk factors mechanisms, such inflammation, oxidative stress, endothelial dysfunction. been implicated either directly or indirectly influencing these phenomena. They secreted by virtually all cell types, cells, cardiomyocytes, stem play critical maintaining vascular homeostasis responding stimuli. Their capacity traverse biological barriers, maintain stability circulation, effectively encapsulate deliver a variety molecular cargos makes them promising candidates both biomarkers therapeutic agents. This review aims explore the multifaceted exosomes CVDs. And we will discuss mechanisms exosome biogenesis release, composition, ways which they contribute disease pathophysiology. Additionally, emphasize potential diagnostic uses, highlighting significance advancement innovative treatment strategies. explores recent findings advancements research, emphasizing CVD paving way future studies clinical applications.

Language: Английский

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Macrophage polarization regulates the pathogenesis and progression of autoimmune diseases

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: 24(7), P. 103820 - 103820

Published: April 21, 2025

Language: Английский

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The Role of Exosomes Derived from Various Sources in Facilitating the Healing of Chronic Refractory Wounds

Pharmacological Research, Journal Year: 2025, Volume and Issue: unknown, P. 107753 - 107753

Published: April 1, 2025

Chronic refractory wounds (CRWs) represent a common and challenging issue in clinical practice, including diabetic foot ulcers, pressure venous arterial ulcers. These significantly impact patients' quality of life may lead to severe consequences such as amputation. Their treatment requires comprehensive consideration both the patient's overall physical condition local wound situation. The major challenges include complex pathogenesis, long cycle, high recurrence rate, heavy economic on patients. Exosomes an emerging therapeutic modality with characteristics low immunogenicity, good biostability, targeting efficiency diseases. derived from different sources exhibit heterogeneity, demonstrating their respective advantages unique properties treatment. This article delves into potential applications mechanisms action exosomes various CRWs, aiming provide new perspectives ideas for management wounds.

Language: Английский

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KCa3.1 Promotes the Migration of Macrophages From Epicardial Adipose Tissue to Induce Vulnerability to Atrial Fibrillation During Rapid Pacing

Canadian Journal of Cardiology, Journal Year: 2024, Volume and Issue: 41(2), P. 195 - 209

Published: Aug. 13, 2024

The relationship between local epicardial adipose tissue (EAT) macrophages and atrial fibrillation (AF) remains unclear. purpose of this study was to investigate the role KCa3.1 in migration from EAT adjacent during rapid pacing. Part 1: Eighteen beagles were randomly divided into sham group, pacing + clodronate liposome (CL) group. 2: TRAM-34 HL-1 cells RAW264.7 co-cultured explore specific migratory mechanism macrophages. Depleting significantly reduced macrophage infiltration atrium induction AF canines with inhibited electrical remodelling Compared those control cells, secretion CCL2 number migrating increased, which could be reversed by TRAM-34. Further vitro experiments showed that regulated through p65/STAT3 signalling pathway. Inhibiting myocardial muscles caused pacing, thereby decreasing vulnerability AF. regulates may related

Language: Английский

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